This application addresses broad Challenge Area (03) Biomarker Discovery and Validation, and specific Challenge Topic, 03-DE-101: Development, Refinement, or Validation of Biomarkers Relevant to Oral or Craniofacial Disorders. The goal of this proposed study is to measure a series of inflammatory biomarkers in saliva and serum to examine to what extent non-invasive salivary biomarkers can be used to characterize those same biomarkers measured in serum. We propose to assess inflammatory biomarkers in saliva and serum samples that are available from previously collected and frozen samples from two funded and completed federally supported studies investigating the association of osteoporosis and periodontal disease (DOD #OS950077;R01DE013505). Samples of saliva and blood were collected, processed and stored using standardized protocols at baseline (DOD study) and again in the same participants prospectively approximately 5 years later (R01). Participants were postmenopausal women recruited into these 2 ancillary studies from the University at Buffalo clinical center of the NIH Women's Health Initiative Observational Study. These stored samples are a unique resource that will be used to measure a panel of inflammatory biomarkers selected for their potential importance in both oral and systemic health. The stored samples were collected at two time points (baseline and 5 years later) at clinic visits. Both saliva and serum blood were collected from these participants on the same day and immediately processed for frozen storage. At these same visits, oral examinations were conducted according to standardized protocols to assess indices of oral and periodontal health (CAL, ACH, bleeding, plaque, calculus, tooth loss, DMFT, oral bone density). Assessments of bone density (DXA), body composition and other physical measures were obtained. Information was collected on participant demographics, personal habits, lifestyle factors, psychosocial factors, dietary intake, physical activity, medication/supplement use, occupation, family history, health practices and medical history. The primary aim of this proposed study is to measure a panel of biomarkers of inflammation in stored saliva samples and determine to what extent salivary levels of these biomarkers are able to characterize these same biomarkers measured in samples of stored serum (N=920). We also propose to determine to what extent the levels of these biomarkers and their relationship to each other change over time (collected at baseline and 5 years later, N=400). In addition, we will determine to what extent baseline markers in salvia and in serum are able to characterize prevalent periodontal disease at baseline, and predict incidence of new and progression of existing periodontal disease (N=920). These data are critically important and significant for several reasons. First, if we are able to characterize serum levels of these biomarkers using saliva, this would provide a novel and non-invasive method of assessing systemic inflammation in older women, which could have many applications. Second, the information collected here will allow us to develop prediction models for incident periodontal disease and also for progression of existing disease. Third, although the focus of this proposed study is to utilize the biomarkers to characterizing periodontal disease, the salivary biomarkers measured in saliva could be used more generally in other chronic diseases thought to be associated with inflammation. For example, in this cohort we would be able to explore salivary biomarkers in the prediction of bone density and osteoporosis which is well characterized in this cohort. We may be able to explore the relation in other chronic diseases that are also assessed as part of routine outcomes collection in WHI. Last, since the cohort is well- characterized according to many variables, effect modification according to factors such as age, BMI, body composition, diet, smoking, presence of subgingival bacteria, and others could easily be explored. The opportunity to use these biomarker data to gain clinical and scientific understanding is enormous and should have substantial impact. There is currently very limited published data available characterizing inflammatory biomarkers in saliva and serum in large well characterized prospective cohorts of women, where both baseline and longitudinal biologic samples are available along with detailed phenotypic information on oral and overall health. This proposed study will add substantially to that body of literature. Importantly, this study aligns well with the 2009-2013 NIDCR Strategic Plan including "integration of molecular, clinical and population health to improve diagnostics and optimize outcomes" and the emphasis on the need to "understand health and disease" from a "systems perspective" that "will require melding these advances with state-of-the-science clinical and epidemiological approaches...". The proposed study will, in a cost efficient way, utilize biologic samples and other data collected from previous federally supported research to expand our scientific understanding of the utility of non- invasive assessments of inflammation in saliva. Ultimately, this information can be used to inform our understanding of the role of inflammation as one mechanism by which periodontal and other chronic diseases occur and progress. Study Relevance: The aim of this study is to measure a panel of inflammatory biomarkers in existing samples of saliva and serum collected from 920 well-characterized postmenopausal women to examine to what extent non-invasive salivary inflammatory biomarkers can be used to characterize those same biomarkers measured in serum, and then determine their association with prevalent and incident periodontal disease. The proposed study will, in a cost efficient way, utilize biologic samples and other data collected from previous research to expand our scientific understanding of the utility of non-invasive assessments of inflammation in saliva. Ultimately, this information can be used to inform our understanding of the role of inflammation as one mechanism by which periodontal and other chronic diseases occur and progress.